Rationale: Compulsive cocaine use is a key feature of cocaine addiction and understanding the factors that promote the development of such a behavior will provide important insights into the mechanism of cocaine addiction and is essential for the clinical management of the disorder.
Objectives: This study aimed to determine how the preexisting compulsive reward-seeking behavior is related to the development of compulsive cocaine-seeking behavior in male and female rats and the potential impact of the reward value and estrous cycle on such behaviors.
Methods: Adult male and female Wistar rats were first trained to self-administer sucrose pellets under a chained schedule, and then, the intensity-response effects of footshock punishment on sucrose SA reinforced by different values of sucrose were measured. Subsequently, the same rats went on to self-administer intravenous cocaine and the punishment intensity-response effects on cocaine SA reinforced by different doses of cocaine were similarly determined. For the female rats, the measurements were made during different phases of the estrous cycle.
Results: The rats showed a wide range of levels of the compulsive behaviors despite the similar training history. Surprisingly, the compulsive sucrose-seeking behavior did not predict the compulsive cocaine-seeking behavior in either sex. Increasing cocaine dose significantly increased the compulsive cocaine-seeking behavior in the female but not male rats. Estrous cycle did not have impact on the compulsive behaviors.
Conclusion: Preexisting differences in compulsive sucrose-seeking behavior do not predict compulsive cocaine-seeking behavior. Compulsive cocaine-seeking behavior is influenced by cocaine dose but not estrous cycle in the female rats.
Keywords: Cocaine; Compulsive behavior; Estrous cycle; Motivation; Self-administration.